title: Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience.
abstract: BACKGROUND
  Carmustine (1,3-bis [2-chloroethyl]-1-nitrosourea, or BCNU) wafers are approved for recurrent glioblastoma and newly diagnosed malignant glioma (MG). Based on considerable clinical experience and use in multimodal regimens, the safety of BCNU wafers needs a re-evaluation.
  
  
  METHODS
  A review of literature from 1996 to February 2008 was conducted on the safety of BCNU wafer in MG patients using search criteria in Medline, EMBASE, and BIOSIS. Abstracts from relevant US and European meetings were also evaluated. Three Phase III (two were pivotal) and 26 non-Phase III studies met inclusion criteria. Overall incidence was estimated for each adverse event (AE), and data from individual studies were summarised as median (range) rates. Comparisons were based on consistent similarities or differences across overall incidence, median rate and range.
  
  
  RESULTS
  BCNU wafer group AE rates from the two pivotal Phase III trials ranged from 4-23% for cerebral oedema, 4-9% for intracranial hypertension, 14-16% for healing abnormalities, 5% for CSF leaks, 4-5% for intracranial infection, 19-33% for seizures, 10% for deep vein thrombosis, and 8% for pulmonary embolus. There were no notable differences in AE rates between the two pivotal Phase III and 26 non-Phase III studies. For the non-pivotal studies, the overall incidence of AEs was low, ranging from 0.2% for intracranial hypertension to 9.6% for healing abnormalities. Healing abnormalities, intracranial infection, and seizures were the most consistently reported AEs, having been observed in 16, 12, and 11 studies, respectively. Rates of healing abnormalities appeared higher in recurrent than in newly diagnosed disease. There were no notable differences between BCNU wafer plus adjuvant treatment (e.g., temozolomide) and BCNU wafer alone, with the exception of haematologic toxicity.
  
  
  CONCLUSIONS
  This review of safety data for BCNU wafers provides reassurance that the AE rates reported in current treatment strategies including multimodal treatment approaches are comparable to those observed in the initial registration studies. The broad range of AE rates may reflect differences in the perioperative and postoperative management. Clinical experience suggests that strategies may exist to reduce the risk of complications.
authors.affiliation: Department of Neurosurgery, Heinrich-Heine-University of Dusseldorf,Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000287:Administration, Topical; D000465:Algorithms; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D002330:Carmustine / Q000008:administration & dosage* / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018849:Controlled Clinical Trials as Topic / Q000706:statistics & numerical data*; D004343:Drug Implants / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005910:Glioma / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D006801:Humans; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004343:Drug Implants; D002330:Carmustine